Synthesis of constrained bicycloalkanes through bibase-promoted brook rearrangement/radical-polar crossover cyclization

• Published in: Chemical science (Cambridge) Vol. 15; no. 28; pp. 1192 - 1198
• Main Authors: Ouyang, Xinke, Shi, Bingyao, Zhao, Yuanyuan, Zhu, Zhimin, Li, Ziyang, Yang, Yuxin, Shu, Chao
• Format: Journal Article
• Language: English
• Published: CAMBRIDGE Royal Soc Chemistry 17.07.2024; Royal Society of Chemistry; The Royal Society of Chemistry
• Subjects: Alcohols; Alkenes; Chemistry; Chemistry, Multidisciplinary; Constraints; Physical Sciences; Science & Technology; Substrates; ALCOHOLS; REACTIVITY; OXETANES; NATURAL-PRODUCTS; STRATEGIES
• ISSN: 2041-6520; 2041-6539
• DOI: 10.1039/d4sc02532f

Highly constrained bicyclic scaffolds are ubiquitous and attracting increasing interest in pharmaceutical and biotechnology discoveries owing to the enhanced activities. Herein, we report a protocol to access highly substituted constrained bicycloalkanes from readily accessible α-silyl alcohols and olefins through a bibase-promoted Brook rearrangement/radical-polar crossover cyclization (RPCC) process. Of note, the practical procedure features broad substrate scope and good group tolerance under mild and operationally simple conditions, using an inexpensive organic photocatalyst. Gram-scale preparation and diverse synthetic transformations demonstrate opportunities to rapidly construct molecular complexity. Mechanistic studies have indicated that the transformation involves a bibase-promoted radical transfer rearrangement addition/radical-polar crossover cyclization relay sequence, which differs from traditional solitary RPCC reactions. A concise protocol for the synthesis of constrained bicycloalkanes has been developed, using easily obtainable α-silyl alcohols and alkenes through a bibase-promoted brook rearrangement/radical-polar crossover cyclization (RPCC) process.